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Biomedical subjects

G Sandrini

Publications and source records attributed to G Sandrini.

At least 19 recordsLinked to original sources

The trigemino-pupillary reflex: a model of sensory-vegetative integration.

Trigeminal stimulation can induce pupillary changes. In vivo and in vitro studies have demonstrated that electrical impulses applied at the trigeminal level can provoke a miotic response, whose nature has been ascribed to the anti-dromic release of neuropeptides (substance P in particular). In order to better define the pupil response to trigeminal stimulation, we investigated the human pupil response to quantified (painless and painful) corneal stimuli by means of a combined (neurophysiological and pharmacological) technique. The response to corneal stimulation was bilateral, direct and consensual. It had a biphasic progression with an initial mydriasis (which directly correlated with the stimulus intensity), followed by a miotic phase. The mydriatic phase disappeared after thymoxamine application, while homatropine pre-treatment prevented occurrence of the miotic phase. The data obtained indicate that the pupillary response to corneal stimulation (trigemino-pupillary reflex) is a multisynaptic reflex with an afferent branch involving the trigeminal system, and an afferent branch involving both the sympathetic and the parasympathetic system. Other pathways, such as the SP-mediated release of acetylcholine, cannot be excluded. Thus the reflex appears to be a potentially useful tool for investigating pain/vegetative interactions in various clinical conditions. In turn, the description of its changes in pathologies characterized by a sympathetic/parasympathetic deficit or by a SP-ergic imbalance will allow us to better describe its inner mechanisms.

Adult

Multimodal evoked potentials in myotonic dystrophy (MyD).

By means of multimodal evoked potentials (EPs), we evaluated the central nervous system (CNS) involvement in 25 subjects suffering from myotonic dystrophy: brainstem auditory evoked potentials (BAEPs), middle-latency auditory evoked potentials (MLAEPs) and somatosensory evoked potentials (SEPs) from the upper limb were performed on all subjects, whereas only the 19 patients, whose clinical ocular abnormalities were slight, underwent pattern-electretinograms (PERGs) and pattern visual-evoked potentials (VEPs) in order to identify the site of lesion among visual pathways (retinal and/or retroretinal). PERGs were abnormal in 8/19 subjects, VEPs in 8/19 subjects (the two techniques were simultaneously abnormal in 8 eyes), BAEPs in 7/25 subjects, MLAEPs in 4/25 subjects (in one subject both BAEps and MLAEPs were abnormal) and SEPs were abnormal in 1/25 subjects. 13/25 of our subjects showed at least one EP that revealed a CNS involvement. The electrophysiological alterations were not correlated either with subject age or with disease duration. Multimodal EPs enabled us to demonstrate that CNS involvement in myotonic dystrophy is important and mainly affects the visual and auditory system.

Adult

Accompanying symptoms of cluster attacks: their relevance to the diagnostic criteria.

Two-hundred-and-fifty-one consecutive cluster headache (CH) patients referred to the Pavia and Parma Headache Centers were evaluated in order to verify the presence and recurrence of one or more autonomic symptoms. Data obtained show that in 2.8% of patients cluster attacks were not accompanied by localized autonomic symptoms, thus confirming the report of Ekbom. We observed a high prevalence of photophobia, nausea and vomiting. The IHS diagnostic criteria for CH may need to be modified. The high frequency of "general" autonomic symptoms seems to suggest a component of "central" drive in the physiopathology of cluster headache.

Adult

Hemicrania continua: a case responsive to piroxicam-beta-cyclodextrin.

The case of a 53-year-old woman is described, who since the age of 38 years had been suffering from a unilateral headache that was at first remitting, but then evolved into an unremitting course. The headache was burning in quality, located in the left forehead and face, and was accompanied by mild ipsilateral autonomic symptoms. The clinical picture, as well as the absolute response to indomethacin, suggested a diagnosis of hemicrania continua. The presence of mild gastric discomfort on continuous indomethacin administration made us transfer the patient to another NSAID (piroxicam-beta-cyclodextrin). With this drug, complete relief and good tolerability was obtained.

Chronic Disease

Central analgesic activity of ibuprofen. A neurophysiological study in humans.

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID). Inhibition of prostaglandin biosynthesis is considered to be the main mechanism of action of this substance. Recently, a central analgesic activity was described in an experimental study. In order to explore the possibility that ibuprofen induces analgesia at central level in humans, we investigated, in a double-blind design, the effects of orally-given 600 mg granular ibuprofen or placebo on nociceptive flexion reflex in normal volunteers. Ibuprofen produced a significant increase, as compared to placebo, in the threshold of the nociceptive reflex. The ratio between subjective pain threshold (Tp) and reflex threshold (Tr) was unchanged after either ibuprofen or placebo administration, indicating that Tp strictly paralleled Tr. These results indicate that ibuprofen displays a central antalgic activity in humans. Different supraspinal structures are probably involved, but the exact mechanisms are still to be clarified.

Administration, Oral

Electrically elicited short and long-latency responses of intrinsic hand muscles in hereditary ataxias. Effects of isometric and ballistic isotonic voluntary contractions.

Short- and long-latency responses (HR and LLR) from thenar muscles were studied in patients with Friedreich's ataxia and pure cerebellar ataxia with later onset by applying electrical stimuli on the median nerve at the wrist. HR and LLR were examined during two different voluntary activities of the opponens pollicis muscle: isometric ("hold") and isotonic ballistic ("move") conditions. A preliminary conventional study of motor and sensory conduction of the median nerve was also carried out. Patients with Friedreich's ataxia had reduced or absent HR and LLR. Furthermore, those who preserved both responses had prolonged HR-LLR interpeak latency. All patients with Friedreich's ataxia also showed peripheral nerve conduction abnormalities, mainly in sensory fibers. These data can be accounted for by the widespread degeneration of many neural structures in this disorder. No abnormalities in HR were observed in pure cerebellar ataxia with later onset, whereas LLR was grossly enlarged in most patients, notably during "move" condition. Since cerebellar structures (especially the cerebellar cortex) are the only ones involved in this disorder, the cerebellum may play a role in modulating LLR. In particular, this effect could be more evident in isotonic ballistic movements.

Adolescent

Cluster headache. Recent developments in clinical characterization and pathogenesis.

The preliminary results of some new studies on cluster headache (CH) point to: (a) the existence of a form, secondary episodic CH, which should be included in the classification of headache; (b) the significant role played by air temperature variations and the number of daylight hours on the onset of CH active periods. Data from the evaluation of pupil response to corneal stimuli suggest a widespread alteration of the pain/autonomic integrative processes at the level of the central nervous system. Finally, data on new preventive (i.e., verapamil and ozone) and symptomatic (i.e., hyperbaric oxygen and sumatriptan) treatments are reported.

Autonomic Nervous System

Devic's neuromyelitis optica: long-term follow-up and serial CSF findings in two cases.

Sixteen cerebrospinal fluid (CSF) specimens serially obtained during long-term follow-up of two patients with Devic's neuromyelitis optica (DNO) were compared with 65 CSF samples from patients with multiple sclerosis (MS). By statistical analysis, the CSF profile in DNO was found to differ from that observed in MS, mainly showing pleocytosis, blood-brain barrier damage, and absence of persistent immunoglobulin G synthesis within the central nervous system. Oligoclonal bands, detected with isoelectric focusing, were present in CSF of 92% of the patients with MS, and in three CSF specimens from one patient with DNO during the first 6 months after disease onset. The bands disappeared in two subsequent samples. This finding has never been described in MS. One patient with DNO had an apparent chronic-relapsing course probably due to steroid dependence. The clinical and CSF features of our cases favour the nosographic independence of DNO and MS.

Adult

A new 5-HT2 antagonist (ritanserin) in the treatment of chronic headache with depression. A double-blind study vs amitriptyline.

The exact relationship between depression and chronic headache remains unclear. Considerable clinical and pharmacological evidence suggests the existence of a common biological terrain. Many antidepressant drugs are effective in the treatment of migraine and chronic headache disorders. Ritanserin, a new very selective serotonin-2 (5-HT2) antagonist, has recently shown both analgesic and antidepressant properties. The present study compares in a double-blind design, the effectiveness of ritanserin and amitriptyline, a well-known antidepressant extensively used in migraine prophylaxis. Thirty-eight patients (30 females and 8 males ranging in age from 20 to 50 yrs) were classified according to the International Headache Society criteria as: patients with chronic tension-type headache (CTH) (11 cases) and patients with coexisting migraine and CTH (MCTH) (27 cases). Only patients with a score equal to or higher than 18 on the Hamilton Rating Scale for Depression (HRSD) were included. Ritanserin was highly effective in reducing Pain Total Index and analgesic consumption in chronic headache, and its activity was similar to that observed during amitriptyline treatment. A significant improvement of HRSD and HRSA (Hamilton Rating Scale for Anxiety) scores was observed during both treatments. The main results of our study concern the demonstration of antiheadache and antidepressive properties of ritanserin. To better define the profile of the patients and their clinical responsiveness to the treatment, dexamethasone suppression test, clonidine test and nociceptive flexion reflex were investigated in our patients. Our data confirm the usefulness of these methods as markers of chronic headache with depression.

Adult

Abnormalities of central motor conduction in asymptomatic HIV-positive patients. Significance and prognostic value.

Percutaneous magnetic stimulation of the brain and spinal cord is a technique developed to demonstrate early and subclinical abnormalities in corticomotoneuron pathways. Central motor conduction time (CMCT) was evaluated in 58 HIV-seropositive patients neurologically asymptomatic (CDC groups II and III) and in two control groups. CMCT was abnormal in about 50% of HIV-seropositive patients. These electrophysiological abnormalities seem to have a negative prognostic value since about 64% of the patients with abnormal parameters seem to progress more rapidly to AIDS stages.

Acquired Immunodeficiency Syndrome

Pupil responsiveness in cluster headache: a dynamic TV pupillometric evaluation.

In this study the variations in pupil diameter induced by different stimuli (dark-light adaptation, light reflex, electric stimulation of the sural nerve) were investigated in episodic (in the active or remission phases) and in chronic cluster headache (CH) patients. Pupil size monitoring was performed with a monocular, infrared TV pupillometer, and sural nerve stimuli were applied after the pain threshold had been measured as the flexion reflex threshold of the biceps femoris muscle (RIII reflex). The results were compared with those obtained in patients with "peripheral" (third neuron) Horner's syndrome and in healthy sex- and age-matched controls. On the symptomatic side we found an impairment of pupil response to light flashes and nociceptive stimuli; similar findings were sometimes evident on the pain-free side, too. These results substantiate previous observations that in cluster headache a dysfunction of the integrative central nervous system pathways also exists intercritically and mostly bilaterally, involving both autonomic regulation and pain perception mechanisms.

Adult

Ritanserin, a serotonin-S2 receptor antagonist, does not prevent 5-hydroxytryptophan-induced beta-EP, beta-LPH and cortisol secretion.

Ritanserin, a new serotonin antagonist selective upon S2 receptor subclass is available. Thus, in order to better define the positive control of serotoninergic pathway on proopiomelanocortin (POMC)-related peptide release, a group of 7 healthy male volunteers has been submitted to a 5-hydroxytryptophane (5-OH-TP) test (200 mg p.o.) before and after 4 days Ritanserin pretreatment. Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol levels were measured hourly for 4 h after each 5-OH-TP loading. Hormonal levels were measured by specific RIAs on extracted (cortisol) and chromatographed (beta-EP and beta-LPH) plasma samples. Basal plasma concentrations of the three hormones were unchanged by Ritanserin pretreatment. Similarly, the integrated areas of beta-LPH, beta-EP and cortisol release in response to 5-OH-TP remained unaffected by the receptor blockade. These data confirm that serotonin-acting drugs are able to stimulate POMC-related peptide release and indicate that such interaction is not mediated through S2 receptor subclass.

5-Hydroxytryptophan

Postprandial and orthostatic hypotension in Parkinson's disease.

In this study, the 24-hour pattern of blood pressure (BP), heart rate, and urinary catecholamine (CA) excretion and the response of BP and plasma CA to the tilt test have been investigated in 13 untreated patients affected by Parkinson's disease (PD) and in 11 age-matched healthy controls. Seven of the 13 PD subjects showed a fall of supine systolic BP greater than that in controls (ie, exceeding 20% of the preprandial value). A significant relationship was found in the PD group between the degree of postprandial hypotension and the 24-hour mean value of dopamine excretion. Eight PD subjects also showed orthostatic hypotension during the tilt test (performed in the morning hours) and in the postprandial phase. Basal norepinephrine plasma levels of PD patients, as well as their percentage increases on standing, were within the range of the controls. These data suggest the existence of a subtype of PD patient, characterized by a widespread impairment of cardiovascular responsiveness and bordering on syndromes of autonomic failure such as progressive autonomic failure or multiple system atrophy, or both.

Aged

Comparative efficacy of cyclandelate versus flunarizine in the prophylactic treatment of migraine.

In a double-blind, parallel-group randomised trial of 3 months' duration, the efficacy of cyclandelate 800 mg twice daily in migraine prophylaxis was compared with that of flunarizine 5mg daily in 40 patients. In comparison with placebo and baseline values, both drugs significantly relieved symptoms of migraine as assessed by indices of pain total index, headache index, analgesic consumption and number of migraine days. Patients taking flunarizine experienced side effects such as drowsiness, weight gain and asthenia, while the most common complaint reported with cyclandelate was gastric upset. These results suggest that cyclandelate may be a useful alternative in migraine prophylaxis.

Adolescent

Evidence for serotonin-S2 receptor involvement in analgesia in humans.

The possible analgesic activity of ritanserin (a new very selective and potent serotonin-S2 antagonist) was studied (double-blind) in humans. A significant increase in nociceptive flexion reflex threshold and subjective pain threshold was observed after five days of treatment, while treatment with placebo did not induce any change. The effects of ritanserin were not reversed by either naloxone or saline (double-blind) administration. Our data suggest a possible role of serotonin-S2 receptors in analgesia.

Adult

Dermorphin inhibits spinal nociceptive flexion reflex in humans.

Dermorphin (D) is a potent opiate-like peptide isolated from the skin of some species of frogs. Experimental studies in animals indicate that D has a potent antinociceptive effect, while no investigation exists about its analgesic properties in humans. Our study shows that i.v. infusion of 0.16 mg/kg D induces a marked and long-lasting increase in the threshold of nociceptive flexion reflex in healthy volunteers. This effect is also evident in a complete chronic spinal subject, showing that D depresses the nociceptive transmission mainly acting at spinal level. Naloxone, while fully antagonizing the effects of morphine and enkephalin analogue, is able to reverse only partly (ca. 50%) the depressive effect of D on nociceptive spinal reflex. This fact may suggest that D interacts with different spinal opiate receptor populations in inducing analgesia.

Adult